First results for datopotamab deruxtecan are reported from TROPION-PanTumor01 Phase I trial for heavily pretreated hormone receptor (HR)-positive, HER2-low breast cancer

Safety results were consistent with previous trials of datopotamab deruxtecan. Results were presented at the 2022 San Antonio Breast Cancer Symposium (abstract #PD13-08).

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca.

In this cohort of TROPION-PanTumor01 (n=41), datopotamab deruxtecan demonstrated an objective response rate (ORR) of 27% as assessed by blinded independent central review (BICR). All responses were partial (n=11) and 56% of patients achieved stable disease (n=23). The disease control rate (DCR) was 85% and median progression-free survival (PFS) was 8.3 months (95% confidence interval [CI], 5.5-11.1). With median follow-up of 13.7 months, the median duration of response (DoR) and the median overall survival (OS) had not been reached with 59% of patients alive for more than one year.

Approximately 70% of breast cancer tumours are considered HR-positive and HER2-low or negative. For patients with HR-positive, HER2-low or negative metastatic breast cancer that progress on or are not suitable candidates for endocrine therapy, the current standard of care is single-agent chemotherapy.

Patients in the TROPION-PanTumor01 trial were heavily pretreated, receiving a median of five lines of prior regimens in the metastatic setting (range 3-10). Prior treatments included CDK4/6 inhibitors (95%), capecitabine (83%), taxanes (59%), anthracyclines (54%), neoadjuvant chemotherapy (37%), mTOR inhibitors (29%) and PI3KCA inhibitors (20%). As of data cut-off on 22 July 2022, five patients remained on study treatment. The safety profile of datopotamab deruxtecan was consistent with previous data with no new safety signals identified. The most common Grade 3 or higher treatment-emergent adverse events (TEAEs) were decreased lymphocyte count (15%), stomatitis (10%), anaemia (7%), dyspnoea (2%) and fatigue (2%). Serious TEAEs were observed in six patients (15%), including one death due to dyspnoea that was not considered treatment-related. Treatment discontinuations due to an adverse event occurred in five patients (12%). No cases of Grade 3 or higher diarrhoea or febrile neutropenia were observed. One case of Grade 3 interstitial lung disease was

TROPION-PanTumor01study : TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicentre Phase I trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumours that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with non-small cell lung cancer (NSCLC) to assess the safety and efficacy of datopotamab deruxtecan to determine the recommended dose for expansion (6mg/kg). The dose expansion part of TROPION-PanTumor01 is enrolling several different cohorts including patients with NSCLC, triple-negative breast cancer (TNBC), HR-positive, HER2-low or negative breast cancer, small cell lung cancer, urothelial, gastric, pancreatic, castration-resistant prostrate and esophageal cancer.

Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, time to response, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.

A comprehensive development programme called TROPION is underway globally with more than 10 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2-targetable tumours, including TNBC, HR-positive, HER2-low or negative breast cancer and NSCLC. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.